Abstract
Carbon–carbon (C–C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C–C bond formation. Strategies that allow C–C bond formation at inert carbon–hydrogen (C–H) bonds enable access to molecules that would otherwise be inaccessible and the development of more efficient syntheses of complex molecules1,2. Here we report a method for the formation of C–C bonds by directed cleavage of traditionally non-reactive C–H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for amide-directed selective C–C bond formation at unactivated sp3 C–H bonds in molecules that contain many such bonds that are seemingly indistinguishable. Selectivity arises through a relayed photoredox-catalysed oxidation of a nitrogen–hydrogen bond. We anticipate that our findings will serve as a starting point for functionalization at inert C–H bonds through a strategy involving hydrogen-atom transfer.
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Acknowledgements
We thank NIGMS (GM80442) for support. J.C.K.C. thanks the Croucher Foundation (Hong Kong) for support. We thank M. Burns (CSU) for technical assistance. We thank R. R. Knowles (Princeton University) for sharing results before publication.
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T.R. and J.C.K.C. conceived the concept and prepared the manuscript. T.R. directed the investigation. J.C.K.C. developed and studied the reaction.
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Nature thanks A. Studer and the other anonymous reviewer(s) for their contribution to the peer review of this work.
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Chu, J., Rovis, T. Amide-directed photoredox-catalysed C–C bond formation at unactivated sp3 C–H bonds. Nature 539, 272–275 (2016). https://doi.org/10.1038/nature19810
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DOI: https://doi.org/10.1038/nature19810
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